Extracellular ATP induces P2X7-dependent nicotinamide phosphoribosyltransferase release in LPS-activated human monocytes:

Innate Immunity

ErikSchilling¹ 

关键词: Monocyte;    NAMPT;    ATP;    P2X7 receptor;    LPS;   

DOI  :  10.1177/1753425912439614

学科分类：生物科学（综合）

来源: Sage Journals

【 摘 要 】

Nicotinamide phosphoribosyltransferase (NAMPT), an enzyme involved in NAD biosynthesis, has recently been identified as a novel mediator of innate immunity.In the present study, we report that treatment of LPS-primed monocytes with ATP greatly enhanced the secretion of NAMPT in a time- and concentration-dependent manner without displaying any cytotoxic effect. NAMPT release was suppressed by pretreatment with the P2X7 receptor (P2X7R) inhibitors oxidized ATP (oxATP) and KN-62, indicating the engagement of P2X7Rs. Furthermore, P2X7R was found to be involved in mediating cell permeability caused by the addition of ATP. To define a role of endogenous ATP in NAMPT secretion, LPS-primed monocytes were incubated in the presence of oxATP and KN-62, as well as the ATP-hydrolyzing enzymes apyrase and hexokinase. With the exception of oxATP, neither substance led to a decrease in NAMPT release, suggesting that autocrine/paracrine ATP is unlikely to be responsible for the LPS-induced release of NAMPT. In conclusion,...

【 授权许可】

CC BY